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Background <p>Implant-associated infections caused by <i>Staphylococcus aureus</i> biofilms remain difficult to eradicate because the extracellular matrix and metabolic heterogeneity jointly suppress antibiotic penetration and immune clearance. The biofilm environment induces excessive interleukin-10 (IL-10) production in dendritic cells, leading to inhibition of the cGAS–STING signaling pathway and T-cell activation. Therefore, strategies that simultaneously disrupt biofilm structure and reverse the immunosuppressive microenvironment are urgently needed.</p> Results <p>We developed a near-infrared–responsive MnO₂@PMS nanoregulator that integrates photothermal catalysis with metabolic immunotherapy. Upon laser irradiation, MnO₂@PMS generated oxygen-independent sulfate radicals (•SO₄⁻) that efficiently degraded the biofilm matrix and suppressed bacterial glutamate metabolism, thereby reducing the synthesis of poly-γ-glutamic acid. This metabolic inhibition decreased biofilm-derived glutamate accumulation and downregulated IL-10 production in dendritic cells, leading to reactivation of the cGAS–STING pathway and restoration of antigen presentation. In vivo, MnO₂@PMS treatment promoted mature dendritic-cell and T-cell activation, reduced bacterial burden, alleviated local inflammation, and enhanced angiogenesis and tissue repair, while exhibiting favourable short-term biocompatibility in vivo.</p> Conclusions <p>This study introduces a glutamate-targeted nanoplatform that couples biofilm destruction with immune reprogramming in a chronic biofilm infection model. By bridging metabolic regulation and immune activation, MnO₂@PMS complements existing nanozyme and photothermal antibiofilm strategies by illustrating a mechanistically supported approach that integrates oxygen-independent sulfate radical catalysis with modulation of glutamate–IL-10–associated immunosuppression.</p> Graphical abstract <p></p>

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Glutamate nanoregulator for metabolic immunotherapy of biofilm-associated implant infections

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月4日

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  • Heng Wu,
  • Jiahao Chen,
  • Xiao Ma,
  • Haijian Li,
  • Qiao Wu,
  • Zhenyu Jiang,
  • Tianyu Xi,
  • Chi Zhang,
  • Geyong Guo,
  • Pei Han

摘要

Background

Implant-associated infections caused by Staphylococcus aureus biofilms remain difficult to eradicate because the extracellular matrix and metabolic heterogeneity jointly suppress antibiotic penetration and immune clearance. The biofilm environment induces excessive interleukin-10 (IL-10) production in dendritic cells, leading to inhibition of the cGAS–STING signaling pathway and T-cell activation. Therefore, strategies that simultaneously disrupt biofilm structure and reverse the immunosuppressive microenvironment are urgently needed.

Results

We developed a near-infrared–responsive MnO₂@PMS nanoregulator that integrates photothermal catalysis with metabolic immunotherapy. Upon laser irradiation, MnO₂@PMS generated oxygen-independent sulfate radicals (•SO₄⁻) that efficiently degraded the biofilm matrix and suppressed bacterial glutamate metabolism, thereby reducing the synthesis of poly-γ-glutamic acid. This metabolic inhibition decreased biofilm-derived glutamate accumulation and downregulated IL-10 production in dendritic cells, leading to reactivation of the cGAS–STING pathway and restoration of antigen presentation. In vivo, MnO₂@PMS treatment promoted mature dendritic-cell and T-cell activation, reduced bacterial burden, alleviated local inflammation, and enhanced angiogenesis and tissue repair, while exhibiting favourable short-term biocompatibility in vivo.

Conclusions

This study introduces a glutamate-targeted nanoplatform that couples biofilm destruction with immune reprogramming in a chronic biofilm infection model. By bridging metabolic regulation and immune activation, MnO₂@PMS complements existing nanozyme and photothermal antibiofilm strategies by illustrating a mechanistically supported approach that integrates oxygen-independent sulfate radical catalysis with modulation of glutamate–IL-10–associated immunosuppression.

Graphical abstract